The goal is to enhance the resolution and contrast of in-vivo images of the rod photoreceptor mosaic taken with high resolution adaptive optics (AO) equipped retinal cameras. There has been great success in imaging other cell types such as the cones, retinal pigment epithelium and leukocytes cells but to date nobody has reported in-vivo evidence for the rods. The project will examine advanced optical techniques that can be combined with AO to further improve the contrast of the retinal images at the spatial scale of the rods and foveal cones. These may be advanced masks to suppress unwanted structure in the images complemented with approaches such as using the Stiles- Crawford effect and deconvolution. Achieving this goal will allow one, for example, to count individual rod cells and calculate cell densities which can then be compared to histological measures. Initially, young, normal subjects will be imaged to refine and optimize the new imaging approaches. As the work progresses, the study will examine diseases that target the rod cells such as retinitis pigmentosa and age related macular degeneration and relate the changes observed to standard clinical tests. This work will lead to better understanding of retinal structure in both normal and diseased eyes. With new drug treatments being developed in animal models, the direct non-invasive imaging of rod cells would provide an important outcome measure when these therapies are transitioned into human clinical trials. PUBLIC HEALTH RELEVANCE: Adaptive optics (AO) has been successfully applied to the human eye to allow imaging of cone photoreceptors in-vivo. With over 120 million rod cells compared to 6 million cones it is surprising that there are no reports of rod imaging in the living eye. The work proposed here will investigate advanced optical techniques to improve the contrast of cone receptor imagery but moreover provide the first in-vivo images of the rod mosaic. Two of the leading causes of worldwide blindness, retinitis pigmentosa (RP) and age related macular degeneration (AMD) first manifest themselves in the rod receptors. When achieved, this work will have tremendous impact into our understanding of how these diseases affect the retinal structure with the potential for earlier disease diagnosis and will be an invaluable tool in the development of new drug therapies.